Contrast agents (CA) are known to depress myocardial function and cause ventricular irritability; therefore investigators have sought to improve CA by changing the ionic content or decreasing osmolarity. The comparative effects of meglumine sodium diatrizoate (MSD), sodium meglumine metrizoate (SMCM), and metrizamide (M) were studied in an isolated canine heart preparation. The parameters observed were coronary blood flow (CBF), myocardial contractile force (MCF), positive and negative dF/dt, and perfusion pressure during normal and ischemic perfusion conditions. MSD had an initial negative inotropic effect but baseline MCF returned in one minute during normal perfusion and two minutes under ischemic conditions. SMCM and M had only a positive inotropic effect under normal perfusion. However, during ischemia, the positive effect of SMCM was followed by a decrease in contractile force at two minutes. M showed only a positive effect on force during ischemia. Our results indicate that calcium additive to negate the depressant effects of CA may be deleterious in the presence of severe coronary artery disease and may increase the risk of coronary arteriography.